Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure

One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients ( n =25, age 1.5–15.5 years) were treated with BTX-A for adductor spasm ( n =12) or pes equinus ( n =13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values ( P  < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores ( P  < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.     

Botulinum toxin A injection for spasticity in diplegic-type cerebral palsy

Botulinum toxin type A can be both safe and effective in relieving spasticity in pediatric patients with cerebral palsy. In our prospective study, we evaluated the functional effect of botulinum toxin A in spastic diplegic-type cerebral palsy. Patients were examined on enrollment and at 1, 3, and 6 months after injection. Passive dorsiflexion of the ankle joint was measured using a goniometer as an angle of possible maximal dorsiflexion with the knee extended and flexed. Spasticity was graded using the Modified Ashworth Scale. Selective motor control at the ankle was assessed, and observational gait analysis was done. The functional status of the patients was determined by using the gross motor classification system. Botulinum toxin A was injected into the gastrocnemius muscle in all patients, and in four patients with concomitant jump knee gait, a hamstring muscle injection was added. Fourteen patients were included in the study. The mean age was 58.81 +/- 15.34 months. Following injection, spasticity was clinically decreased and statistically significant improvement was noticed in all clinical parameters after 1, 3, and 6 months of injection. The improvement in the clinical parameters decreased after 6 months but not to the baseline. One patient was Level II, four patients were Level III, and six patients were Level IV according to the Gross Motor Function Classification System at baseline. Improvement in the gross motor classification system is continued after 6 months in 12 children. The main goal of spasticity treatment in cerebral palsy is functional improvement. In our study, most of our patients had functional improvement according to the gross motor function classification system and did not change at 6 months.     

不同定位方式下不同剂量肉毒毒素治疗痉挛性脑瘫的疗效观察

目的 观察不同定位方式下靶肌肉注射不同剂量A型肉毒毒素(BTX-A)治疗儿童痉挛性脑瘫的疗效.方法 选择厦门市妇幼保健院儿童神经康复科收治的痉挛性脑瘫患儿120例,分别应用肌电图定位及反向徒手牵拉定位(各60例),再分别按痉挛肌肉局部注射BTX-A剂量(3 U/kg、4 U/kg及5 U/kg)各分为3组(各20例),注射后配合康复训练.随访3个月时患儿疗效,采用粗大运动评价最表(GMFM)评定患儿功能区的运动功能,改良Ashworth痉挛量表评定肌痉挛程度.结果 肌电图定位组较反向徒手牵拉定位组治疗后GMFM评分增加和Ashworth分级减轻,差异有统计学意义(P<0.05),但此两种定位方式下各不同剂量BTX-A组间治疗后GMFM评分和Ashworth分级差异无统计学意义(P>0.05).结论 在相同有效剂量BTX-A注射情况下,肌电图定位较反向徒手牵拉定位疗效更好.

Abstract：

Objective To observe the clinical effects of different doses of botulinum toxin A (BTX-A) and different lacation ways on children with spastic cerebral palsy. Methods One hundred and twenty patients with BTX-A were employed in our study;these patients were performed locations of electromyography (n=60) and reverse stretching hand (n=60), and then, they were equally sub-divided into 6 groups, respectively: receiving injection of BTX-A at doses of 3, 4 and 5 U/kg, respectively (n=20).After injection, they were commenced functional training for 3 months. The gross motor assessment scale (GMFM) was used to assess the motor function of functional areas in these children 3 months after the training. The modified Ashworth scale was used to assess the degree of muscle spasticity. Results The scores of GMFM in patients received treatment with location of electromyography increased as compared with those with reverse stretching hand (P< 0.05), but the scores had no statistically significances among different doses of BTX-A treatment groups (P> 0.05). The Ashwort grade in patients received treatment with location of electromyography alleviated as compared with those with reverse stretching hand (P<0.05), but no statistically significance of grading was noted among different doses of BTX-A treatment groups (P>0.05). Conclusion All parameters in patients received treatment with location of electromyography improve better than those with reverse stretching hand after injection of same dose of BTX-A.     

Functional outcomes of multilevel botulinum toxin and comprehensive rehabilitation in cerebral palsy

The objective of this study was to measure the effect of lower extremity multilevel botulinum toxin A injections and comprehensive rehabilitation on spasticity and to determine the functional gains in ambulatory children with cerebral palsy. Sixteen ambulatory children with spastic cerebral palsy (9 hemiplegic, 7 diplegic), aged between 3 and 8 years, who were able to walk with or without assistance (Gross Motor Functional Classification System I-III) were recruited to the study. Botulinum toxin A injections were applied to a total of 23 extremities, followed by a comprehensive rehabilitation program. Walking distance and walking speed (evaluated by the Six-Minute Walk Test) were significantly improved after treatment. Similarly, scores on the Observational Gait Scale (assessed by video gait analysis) increased significantly. Improvements in muscle length, spasticity, and selectivity were recorded. Reduced muscle spasticity after botulinum toxin A injections in children with cerebral palsy, with a comprehensive rehabilitation program, enabled clinically relevant improvements in functional ability.     

The use of botulinum toxin type A treatment in children with spasticity

The current modalities in managing spastic children have some limitations; thus, alternative therapeutic agents are in need. The purpose of this study is to investigate whether intramuscular botulinum toxin type A administration may be an alternative agent in the treatment of children with cerebral palsy. Eighteen children who were aged between 3 and 17 years and manifested cerebral palsy were administered intramuscular botulinum toxin type A with a total dose of 6 U/kg body weight. Outcome measurements were determined with four methods, including Ashworth Spasticity Scale, standardized videotape assessments, observational gait analysis, and walking velocity. Ashworth Spasticity Scale and videotape assessments were statistically significant before and after treatment in all muscles (P < 0.001). The best improvement in video gait analysis was evident at week 8. The botulinum toxin type A injections yielded an improved walking velocity at all visits. The observational gait analysis and walking velocity demonstrated an improvement after treatment in the gastrocnemius-injected group (P < 0.001). In conclusion, intramuscular botulinum toxin type A administration may be effective in children with cerebral palsy, especially at week 4 and when injected in gastrocnemius.     

Botulinum toxin type A for the treatment of the spastic equinus foot in cerebral palsy

Muscle overactivity, one of the cardinal features of spasticity, is a common sequel of cerebral palsy. In this group of patients spasticity is responsible for several limitations that interfere with gait, causing variable functional disability. Drugs such as baclofen, tizanidine, or benzodiazepines, or even definitive treatments such as orthopedics or neurosurgeries are generally prescribed with uncertain results. The use of botulinum toxin type A has been frequently suggested for the treatment of spastic equinus foot in cerebral palsy, but few studies with adequate methodology support this idea. The present paper reviews and summarizes the data of published double-blind, randomized clinical trials to assess, with a meta-analysis, if botulinum toxin type A is an adequate treatment for spasticity caused by cerebral palsy. The results reveal a statistical superiority of botulinum toxin type A over placebo on gait improvement, tested using the Physician Rating Scale and Video Gait Analysis (Peto odds ratio = 3.99, 95% confidence interval = 2.20-7.22) in patients with spastic equinus foot. The botulinum toxin group also presented better results in the subjective assessment than the placebo group (Peto odds ratio = 3.49, 95% confidence interval = 1.50-8.12). Adverse events were more frequently observed after the use of botulinum toxin type A, but they were considered mild and self-limited.     

Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: an open-label, dose-escalation pilot study

Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of I or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.     

自体骨髓间充质干细胞回输对脑性瘫痪儿童运动功能发育的影响

背景：自体骨髓干细胞对神经系统疾病具有一定的治疗作用,但对脑瘫治疗缺乏系统有对照的临床研究。 目的：分析自体骨髓间充质干细胞移植对脑性瘫痪儿童运动功能发育的影响。 方法：将34例脑性瘫痪者按其家长是否同意使用自体骨髓干细胞移植治疗分为治疗组和对照组,治疗组采取自体骨髓间充质干细胞移植结合康复训练,对照组只采用康复训练,分别在治疗前和治疗后3个月做粗大运动功能测试量表(GMFM)评估并进行对比。 结果与结论：与治疗前比较,2组治疗后3个月GMFM评分均增高,而GMFM评分增加量均降低,差异均有显著性意义 (P < 0.05)。治疗组GMFM评分增加量高于对照组(P < 0.05)。 提示自体骨髓间充质干细胞移植治疗脑性瘫痪是有效的,对促进脑性瘫痪患儿运动功能发育有积极作用。     

Botulinum toxin a in management of cerebral palsy

The efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in children with cerebral palsy was studied in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. Fifteen children with cerebral palsy (mean age: 6 years, 8 months) were included in the study. All had limb deformities associated with nonfixed joint contractures that had not responded to physical therapy. Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while barefooted. The study provides evidence that the intramuscular injection of botulinum toxin A in selected skeletal muscles decreases muscle tone and contractures, and increases range of motion and motor function.     

Upper limb function after botulinum toxin A treatment in cerebral palsy: Two years follow-up of six cases

The objective of this study was to investigate the effects of botulinum toxin A (BTXA) treatment on impairment and function of the upper limb during a 2-year follow-up period. A prospective longitudinal study design with assessments before and after intervention was utilized, involving six patients with cerebral palsy (three boys and three girls) aged 3 years 4 months to 11 years 11 months at commencement of study. The outcome measures were spasticity (modified Ashworth, MAS), active and passive range of movement (ROM), grips (pinch, key grip, 3-finger grip, narrow cylinder grip, wide cylinder grip, pen grip and diagonal grip; grasping, releasing; pronation-supination), bimanual functions, fine motor functions (Melbourne Assessment of Unilateral Upper Limb Function), movement pattern (Upper Limb Physician's Rating Scale, ULPRS), functional skills and self-care capability (Paediatric Evaluation of Disability Inventory, PEDI), upper extremity use (House Classification) and cosmetic appearance. The assessments were repeated by the same examiners at baseline and at 1, 3 and 6 months after each BTXA treatment and then every 6 months until 24 months. One subject received a total of four injections (at 0, 6, 12 and 18 months), one two injections (at 0 and 12 months) and four one injection at the beginning of the study period. Upper extremity surgery was performed on two subjects during the study and one was operated on 2 months after completion of the study. All children benefited from the BTXA treatment in terms of reduction in muscle tone and increase in active and passive ROM. By 6 months, spasticity returned, but in four children passive and especially active ROM remained better than at baseline. No significant changes in grips, bimanual tasks or Melbourne Assessment scores were detected. The change in movement pattern (ULPRS) was maintained for 3 months in two children and beyond this in four, thus extending beyond the pharmacologic effects of botulinum toxin A. All but one child showed improvement in PEDI functional skill and caregiver assistance scale scores during the 2-year period. The House classification showed a one-grade improvement in one child at 1 month and in one child at 3 months and a three-grade improvement in one child at 3 months after BTXA treatment. After each treatment, the parents reported at least a one-grade improvement in cosmetic appearance in all children at 1 month and in four children maintained at least until 6 months. In two subjects operated during the study period, a distinct improvement in active and passive ROM and a two-grade improvement in the House classification were observed after the operation. In this limited series, the reduction in muscle tone after BTXA treatment did not translate into better gripping or quality of fine motor functions (Melbourne Assessment) of the affected hand, but seemed to have a positive effect on upper limb movement pattern (ULPRS), upper extremity use (House Classification) and cosmetic appearance. Assessment of upper limb function in a child with cerebral palsy demands a variety of measures.